Histoplasmosis is an endemic mycosis caused by Histoplasma capsulatum. Infection develops by inhalation of microconidia from environmental sites inhabited by birds and bats. Disseminated disease is the usual presentation due to impaired cellular immunity. Common clinical manifestations include fever, fatigue, malaise, anorexia, weight loss, and respiratory symptoms. Histoplasma antigen detection is the most sensitive method for diagnosis. The sensitivity of the MVista ® Quantitative Histoplasma antigen enzyme immunoassay is 95-100% in urine, over 90% in serum and bronchoalveolar lavage (BAL) antigen and 78% in cerebral spinal fluid (CSF). A proven diagnosis can be established by culture or pathology with sensitivities between 70% and 80%. The sensitivity of antibody detection by immunodiffusion or complement fixation was between 60% and 70%. Diagnosis using molecular methods has not been adequately validated for implementation and FDA cleared assays are unavailable. Liposomal amphotericin B should be used for 1-2 weeks followed by itraconazole for at least one year until CD4 counts are above 150 cells/mm3, HIV viral load is below 400 copies/mL and Histoplasma urine antigen is negative. Serum itraconazole level should be monitored to avoid drug toxicity. Antigen should be measured periodically to establish that treatment is effective and to assist in identifying relapse. The incidence of immune reconstitution inflammatory syndrome is low but it must be considered in patients who are thought to be failing antifungal treatment as it does not respond to changing antifungal agents but rather to initiation of corticosteroid therapy. In this review, we discuss pathogenesis, clinical manifestations, diagnosis and treatment based on personal experience and relevant publications.

No abstract

Background Blastomycosis is an endemic fungal infection that causes pulmonary and systemic disease. It can occur irrespective of the patient's immune status. The risk factors associated with the severity of the disease are not well studied. Methods This is a retrospective study of patients admitted with blastomycosis at the University of Kentucky Hospital from 2004 to 2019. Logistic regression was used to identify variables associated with severe blastomycosis. Results A total of 76 patients were identified; 22 (28.9%) had at least one immunosuppressive condition. Pulmonary blastomycosis was reported in 49/76 (65%) of the patients and disseminated infection in 27/76 (35.5%). All diagnostic tests were not significantly different in diagnostic results in immunocompromised vs immunocompetent patients. Cultures and histopathology were positive in 56/61 (91.8%) and 54/63 (85.7%) respectively. Blastomyces or Histoplasma antigen test was positive in 13/17 (76.4%) in immunocompromised patients compared to 26/42 (61.9%) in immunocompetent patients. Immunocompromised patients were more likely to be admitted to the hospital and ICU compared to immunocompetent patients. In the multivariate analysis, pulmonary multilobar disease (RR 5.68; 95% CI 2.13–15.15), obesity (RR 2.39; 95% CI 1.26‐4.51), diabetes mellitus (RR 3.50; 95% CI 1.38‐8.90) and immunosuppression (RR 2.28; 95% CI 1.14‐4.56) were significant independent risk factors for severe blastomycosis. Inpatient mortality proportion was higher in immunocompromised patients but not statistically significant. Conclusion Pulmonary multilobar disease, obesity, diabetes mellitus and immunosuppression were risk factors associated with severe blastomycosis. Immunocompromised patients required more frequent hospitalisations compared to immunocompetent patients.

Background The Intravenous Drug Use (IVDU) epidemic has been developing into a public health crisis in the last twenty years. As a result, the incidence of severe bacterial infections such as infective endocarditis (IE) has been rising dramatically. Methods Cross-sectional study, we reviewed records of all admissions to University of Kentucky hospitals with IVDU associated ICD9/10 codes who received an Infectious Diseases consult during 2018 and focused on the cases with a diagnosis of IE. We describe associated epidemiologic, clinical, and microbiological features Results We include 391 patients in this cohort, among those 157 patients were for IE. Patients had a median age of 34 years old (range: 20 - 62); 81 (51.5%) were female, and five (6.1%) were pregnant and 153 (97.4%) identified as white. A previous episode of infective endocarditis was reported in 55 (35%) cases. The most common illicit substances used were heroin 68 (43.3%) and methamphetamine 65 (41.45%). Tobacco abuse was reported in 134 (86.4%) cases. Fever reported in 93 (59.8%) cases, shortness of air in 43 (28.0%) cases, and chest pain in 44 (28.6%) cases were the most common symptoms. Hepatitis C antibody was positive in 115/149 (73.2%) and 3/143 (1.9%) were HIV positive. Right-sided IE was more frequent, the tricuspid valve was involved in 94 (59.8%) patients. Gram-positive pathogens were isolated in 139 (88.5%) patients, Staphylococcus aureus was isolated in 102 (64.9%) patients, of which 67 (65.7%) were methicillin resistant. Gram-negative pathogens were isolated in 18 (11.2%) patients. Eighty-eight (56.4%) patients had an addiction medicine consult during their admission, (22.9%) patients left against medical advice and 20 (12.7%) patients needed to be readmitted within 30 days after discharge. Overall mortality was 12.7% and was significantly associated with infection by gram-negative pathogens (RR: 2.5; CI 95% 1.05 – 6.25, p=0.037). Conclusion Infectious endocarditis is a frequent complication in PWID which carries a high risk of mortality and often involves the tricuspid valve. The most common pathogen isolated was S. aureus, isolation of gram-negative pathogens was associated with increased mortality. Disclosures All Authors: No reported disclosures

Background Blastomycosis is an endemic dimorphic fungal infection caused by Blastomyces dermatitidis. The risk factors associated with severe presentation are not well defined. Methods Retrospective study of patients treated for blastomycosis at the University of Kentucky Hospital from 2004-2019. Statistical analyses were performed with STATA version 12.0 (College Station, Texas). Logistic regression was used to identify variables associated with severe infections. Results Among 82 patients, median age was 48 years old (range: 16 - 89); 66 (80.5%) were male and 71 (92.2%) were white, 25/77 (32.4%) were obese, 24 (29.2%) were diabetic, 21 (25.6%) had COPD, 26 (31.7%) had at least one immunosuppressive condition. The median duration of illness was 86 (3-365) days. 37 (45.1%) had cough and 35 (42.6%) had dyspnea 19 (23.1%) patients were treated in the ICU, 42 (51.3%) in non-ICU inpatient wards, and 21 (25.6%) in an outpatient setting. Cultures were obtained in 69 cases, 59 (85.5%) reported as positive, KOH stain positive in 30/61 (49.1%). Histopathology was positive in 48/66 (72.7%) samples. Urine Histoplasma or Blastomyces antigen was positive in 41/58 (70.6%), and Serum Histoplasma or Blastomyces antigen was positive in 22/34 (64.7%). Among 64 (78.0%) patients with pulmonary blastomycosis, acute and chronic pneumonia were 16 (25.0%) and 12 (18.7%) cases respectively, and nodular lung lesions were reported in 36 (56.2%). Initial antifungal treatment was amphotericin B liposomal in 38/80 (47.5%), overall mortality was 11 (13.4%). A multivariable analysis was performed to find predictors of severe blastomycosis infection, no association was seen with factors as male sex (IRR 1.96; 95%CI 0.84 – 4.55), and was confirmed that significant independent associated risk factors for severe infection were age older than 50 (IRR 3.5; 95%CI 1.42-8.83), obesity (IRR 3.1; 95% CI 1.41-6.87), diabetes (IRR 2.5; 95% CI 1.16-5.50), leukocytosis (IRR 1.03; 95%CI 1.00-1.07) and anemia (IRR 3.0; 95% CI 1.55-5.85). Conclusion Pulmonary Blastomycosis is the most common presentation. Culture and histopathology are more sensitive than antigen assay. Independent factors associated to severe disease were older age, obesity, diabetes, and anemia at admission. Disclosures All Authors: No reported disclosures

Background Serum (1-- >3)-b-D-glucan (BDG) assay is a noninvasive serological marker that can be used as an adjunct to the diagnosis of invasive candida infections, Pneumocystis jiroveci pneumonia (PJP) as well as aspergillosis. There is limited data in serial monitoring of serum BDG in those fungal infections after treatment was initiated. Figure 1:Serial serum BDG levels of each subject after treatment initiation Methods This is a cross-sectional study of subjects with proven fungal infection (invasive candidiasis, aspergillosis or PJP) and with increased serum BDG >500 pg/ml who were admitted to University of Kentucky (UK) hospitals or clinics from 01/2012 to 01/2021. It was approved by institutional IRB. We compared at least two measures of the serum β-D-glucan levels obtained within two to eight weeks after initial diagnosis to evaluate the levels of β-D-glucan during and post-treatment. A decrease in BDG level is defined as any value below 500 pg/ml; normal serum BDG level as < 80 pg/ml. Results Of 26 subjects included in this cohort, 14 (51.8%) subjects had invasive candidiasis, six (22.2%) subjects had PJP, and six (22.2%) subjects had invasive aspergillosis. Twelve patients did not have a repeat BDG level after at least two separate levels with >500 pg/ml. Ten (38.5%) subjects had a decline in BDG level 2-3 weeks after starting treatment. Serum BDG level did not return to within normal limits at week 4 of treatment except one patient. A repeat serum BDG level was seen decline at three weeks of treatment in four of six (66.6%) subjects with PJP, six weeks of treatment in three of six (50.0%) subjects with invasive aspergillosis and 8 weeks of treatment in six of 14 (42.8%) patients with invasive candidiasis. Two subjects had persistent elevation of BDG 8 weeks after treatment. (Figure 1) Conclusion Serial serum BDG level was not routinely done for monitoring the treatment response in this cohort. There was no linear decline in serum BDG level even after appropriate treatment in invasive fungal infections. A decline in serum BDG level was best observed among subjects with PJP pneumonia. It appears that the duration of a decline in serum BDG level was shorter in patients with PJP and longer in patients with invasive candidiasis. Disclosures All Authors: No reported disclosures.

BackgroundEffective care for persons living with HIV (PLWH) requires a coordinated, multi-disciplinary approach that includes social workers, physicians, advanced practice providers, pharmacists, social workers and community outreach workers. Unfortunately, these individuals often work and train independently of one another without a full sense of the responsibilities and contributions of others. Too often, this results in fragmented or ineffective care.MethodsIn response to the need to improve exposure to both HIV and coordinated interdisciplinary care, the Kentucky AIDS Education and Training Center at the University of Kentucky developed the HIV Interprofessional Education (IPE) Program in 2016. This dynamic IPE links students in multiple professional training programs (including pharmacy, medical, social work, and physician assistant students) to a year-long curriculum designed to acquire advanced skill sets for the treatment of HIV/AIDS. This curriculum includes inpatient and outpatient shadowing opportunities with multiple departments, didactic seminars, flexible mentored learning, and a collaborative capstone project designed to impact the local HIV community.ResultsWe report on the development of this program as well as a comprehensive assessment of the quantitative and qualitative experiences of our trainees. Participants reported significant improvements in their understanding of not only the complexities of the continuum of care for PLWH but also on how to improve care by enhancing collaboration between disciplines. They also reported development of critical and generalizable skills including taking a social history, addressing co-morbid mental health and substance abuse issues, cultural competency, screening and prevention strategies for HIV. ConclusionAs we strive to provide comprehensive and effective care for PLWH aimed at achieving the goals of universal test and treat and retention in care, we must find way to improve crosstalk and understanding of the interdisciplinary nature of modern medical care. Ideally, this begins during training. We present our experience in the development of a novel and highly effective program which has spanned multiple departments and has substantially impacted the approach to HIV care in our trainees. Disclosures All authors: No reported disclosures.

Introduction The Affordable Care Act (ACA) enacted on March 23, 2010 significantly impacted access to healthcare for people living with HIV (PLWH). Expansion of care was accomplished in three areas: eliminating exclusions for pre-existing conditions, elimination of lifetime caps on healthcare expenditures, and expansion of Medicaid eligibility. Purpose This study evaluated the impact of state implementation of the ACA Medicaid expansion on referral to HIV care at a Ryan White federally funded clinic in Kentucky (University of Kentucky Bluegrass Care Clinic [UK BCC]). Methods Retrospective chart review of all newly enrolled patients at the UK BCC between March 2010 and June 2017. Data included patient demographics and referral source, and were divided into two groups to compare enrollments before and after Kentucky implemented the ACA Medicaid expansion. Data were collected from 2018–2019 and analyzed in 2020. Results Following Medicaid expansion there were statistically significant changes in the patterns of referral to federally funded HIV care. These included a significant decrease in the proportion of referrals from state and local health departments, and an increase in both proportion of referrals from outpatient clinics and transfers from different HIV care providers. Implications These results have implications for engaging more PLWH into HIV care, particularly in states where patients have increased access to screening and assessment of risk at primary care encounters through implementation of the ACA Medicaid expansion.